Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway

doi:10.1016/j.bbrc.2005.04.044

Biochemical and Biophysical Research Communications

Volume 331, Issue 4, 17 June 2005, Pages 1245-1252

https://doi.org/10.1016/j.bbrc.2005.04.044 Get rights and content

Abstract

Elderly lung cancer patients and those with poor performance status/co-morbid conditions are deprived of chemotherapy because of high toxicity of multidrug regimens. Human squamous cell lung carcinoma H520 cells treated with Curcumin were sensitized to the cytotoxicity caused by chemotherapeutic agent, Vinorelbine. Both caused apoptosis by increasing the protein expression of Bax and Bcl-xs while decreasing Bcl-2 and Bcl-X_L, releasing apoptogenic cytochrome c, and augmenting the activity of caspase-9 and caspase-3. Expression of Cox-2, NF-κB, and AP-1 was also affected. 23.7% apoptosis was induced in the H520 cells by treatment with Curcumin while Vinorelbine caused 38% apoptosis. Pre-treatment with Curcumin enhanced the Vinorelbine induced apoptosis to 61.3%. The findings suggest that Curcumin has the potential to act as an adjuvant chemotherapeutic agent and enhance chemotherapeutic efficacy of Vinorelbine in H520 cells in vitro. Thus, Curcumin offers the prospect of being beneficial in the above-mentioned patient groups.

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Materials and methods

Cell culture and treatments. Human NSCLC (squamous cell carcinoma) cell line NCI-H520 was maintained in DMEM (Sigma) supplemented with 10% fetal calf serum and antibiotics in a humidified atmosphere of 5% CO₂ in air at 37 °C [17]. Logarithmically growing cells were treated with Curcumin (Sigma), Vinorelbine (a gift from Dabur Oncology Division, New Delhi, India), and a combination of the two for various time periods. Curcumin stock solutions were made up in dimethyl sulfoxide (DMSO) (Sigma);

Pre-treatment of H520 cells with Curcumin enhances the apoptosis induced by Vinorelbine

MTT assay showed that Curcumin alone (24 h) induced 29.8 ± 2.1% (p = 0.013) cytotoxicity, Curcumin (48 h) induced 30.5 ± 2.2% (p = 0.023) cytotoxicity while Vinorelbine alone induced 36 ± 2.16% (p = 0.005) cytotoxicity. Priming the cells with 25 μM Curcumin for 24 h prior to treatment with 0.1 μg/ml Vinorelbine (for 24 h), increased the cytotoxicity to 64.4 ± 3.2% (p = 0.010 with Curcumin alone (48 h) and p = 0.003 with Vinorelbine alone) (Fig. 1F). Distinct morphological changes characterized by membrane blebbing,

Discussion

Search for new chemopreventive and antitumor agents that are more effective but less toxic has kindled great interest in phytochemicals. Curcumin, derived from the plant Curcuma longa, is one such compound which was used in this study. It has been shown to inhibit the growth of a wide variety of tumor cells in multiple experimental model systems [21] but little is known about its potential as an adjuvant chemotherapeutic agent. It has been reported that Curcumin, an antioxidant, inhibits

Acknowledgments

The authors are grateful to Department of Biotechnology, New Delhi, India, for financial support and Dabur (Oncology division), New Delhi, India, for providing Vinorelbine.

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